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Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency
Combined pituitary hormone deficiency represents a disorder with complex etiology. For many patients, causes of the disease remain unexplained, despite usage of advanced genetic testing. Although major and common transcription factors were identified two decades ago, we still struggle with identific...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461210/ https://www.ncbi.nlm.nih.gov/pubmed/32796691 http://dx.doi.org/10.3390/ijms21165757 |
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author | Budny, Bartłomiej Karmelita-Katulska, Katarzyna Stajgis, Marek Żemojtel, Tomasz Ruchała, Marek Ziemnicka, Katarzyna |
author_facet | Budny, Bartłomiej Karmelita-Katulska, Katarzyna Stajgis, Marek Żemojtel, Tomasz Ruchała, Marek Ziemnicka, Katarzyna |
author_sort | Budny, Bartłomiej |
collection | PubMed |
description | Combined pituitary hormone deficiency represents a disorder with complex etiology. For many patients, causes of the disease remain unexplained, despite usage of advanced genetic testing. Although major and common transcription factors were identified two decades ago, we still struggle with identification of rare inborn factors contributing to pituitary function. In this report, we follow up genomic screening of CPHD patient cohort that were previously tested for changes in a coding sequences of genes with the use of the whole exome. We aimed to find contribution of rare copy number variations (CNVs). As a result, we identified genomic imbalances in 7 regions among 12 CPHD patients. Five out of seven regions showed copy gains whereas two presented losses of genomic fragment. Three regions with detected gains encompassed known CPHD genes namely LHX4, HESX1, and OTX2. Among new CPHD loci, the most interesting seem to be the region covering SIX3 gene, that is abundantly expressed in developing brain, and together with HESX1 contributes to pituitary organogenesis as it was evidenced before in functional studies. In conclusion, with the use of broadened genomic approach we identified copy number imbalances for 12 CPHD patients. Although further functional studies are required in order to estimate its true impact on expression pattern during pituitary organogenesis and CPHD etiology. |
format | Online Article Text |
id | pubmed-7461210 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74612102020-09-14 Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency Budny, Bartłomiej Karmelita-Katulska, Katarzyna Stajgis, Marek Żemojtel, Tomasz Ruchała, Marek Ziemnicka, Katarzyna Int J Mol Sci Communication Combined pituitary hormone deficiency represents a disorder with complex etiology. For many patients, causes of the disease remain unexplained, despite usage of advanced genetic testing. Although major and common transcription factors were identified two decades ago, we still struggle with identification of rare inborn factors contributing to pituitary function. In this report, we follow up genomic screening of CPHD patient cohort that were previously tested for changes in a coding sequences of genes with the use of the whole exome. We aimed to find contribution of rare copy number variations (CNVs). As a result, we identified genomic imbalances in 7 regions among 12 CPHD patients. Five out of seven regions showed copy gains whereas two presented losses of genomic fragment. Three regions with detected gains encompassed known CPHD genes namely LHX4, HESX1, and OTX2. Among new CPHD loci, the most interesting seem to be the region covering SIX3 gene, that is abundantly expressed in developing brain, and together with HESX1 contributes to pituitary organogenesis as it was evidenced before in functional studies. In conclusion, with the use of broadened genomic approach we identified copy number imbalances for 12 CPHD patients. Although further functional studies are required in order to estimate its true impact on expression pattern during pituitary organogenesis and CPHD etiology. MDPI 2020-08-11 /pmc/articles/PMC7461210/ /pubmed/32796691 http://dx.doi.org/10.3390/ijms21165757 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Budny, Bartłomiej Karmelita-Katulska, Katarzyna Stajgis, Marek Żemojtel, Tomasz Ruchała, Marek Ziemnicka, Katarzyna Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency |
title | Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency |
title_full | Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency |
title_fullStr | Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency |
title_full_unstemmed | Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency |
title_short | Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency |
title_sort | copy number variants contributing to combined pituitary hormone deficiency |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461210/ https://www.ncbi.nlm.nih.gov/pubmed/32796691 http://dx.doi.org/10.3390/ijms21165757 |
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